Steroids to reduce the impact on delirium (STRIDE): a double-blind,randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture

Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9–17.6 [1.8–139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3–6 [3–7]) vs. 9 (6–13 [5–14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22–1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design.     

Relationships Between Mycoplasma pneumoniae and Human Respiratory Epithelium

The interaction was studied between Mycoplasma pneumoniae and its natural host cell, the human respiratory epithelium. Organized, ciliated cells provided by fetal trachea in organ culture enabled examination of the host-parasite relationship by light, immunofluorescence, and electron microscopy. Impairment of cellular function was reflected by disorganization and loss of ciliary motion; this was associated with a sequence of cytopathological changes denoting progressive cell injury. The organisms were found concentrated on the luminal surface of ciliated epithelium and cells lining the submucosal glands. A differentiated portion of the Mycoplasma, consisting of an extension of the unit membrane containing an electron-dense core surrounded by a lucent space, served as the means of attachment to host cells. The findings suggest that the pathogenicity of M. pneumoniae depends upon intimate extracellular infection with production of functional and structural changes initiated by host cell membrane injury.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Chest pain with nondiagnostic electrocardiogram in the emergency department: a randomized controlled trial of two cardiac marker regimens

BACKGROUND: Early detection of acute myocardial infarction (AMI) may save lives. In the emergency setting, it is unclear whether the early use of certain cardiac markers (myoglobin and cardiac troponin I [cTnI]) assists in making appropriate decisions whether to admit or discharge patients with chest pain of possible ischemic cause who have nondiagnostic electrocardiograms (ECGs). We performed a study to determine whether the addition of new cardiac markers in the emergency department results in improved clinical decisions. METHODS: A single-blind randomized controlled trial was conducted between June 1997 and June 1998 in a tertiary care emergency department in Kingston, Ont. Of 296 patients aged 30 years or more who presented to the emergency department with chest pain and nondiagnostic ECGs, 146 were randomly assigned to the intervention group (determination of baseline creatine kinase [CK] level, CK MB fraction and cTnI level, and myoglobin level at baseline and at 2 hours) and 150 to the control group (determination of baseline CK level and CK MB fraction). Outcome measures included the rate of admission to the inpatient cardiology service and length of stay in the emergency department. RESULTS: Of the 296 patients, 34 (11.5%) received a diagnosis of AMI in the emergency department, and 92 (31.1%) had chest pain of noncardiac cause. Patients in the intervention group were less likely than those in the control group to be admitted to the cardiology service (67 [45.9%] v. 81 [54.0%]). The absolute difference in the proportion (8.1% [95% confidence interval -3.3 to 19.5]), although potentially important clinically, was not statistically significant. The length of stay in the emergency department was essentially the same in the 2 study groups. At 30 days, the proportions of patients with a diagnosis of recurrent angina (58.2% in the intervention group and 58.0% in the control group) and AMI (12.3% and 14.7%) were also similar. INTERPRETATION: The optimal cardiac marker panel to be used in the emergency department remains unknown. The addition of serial testing of myoglobin with cTnI confirmation to the standard panel did not substantially change the clinical management or outcomes of patients presenting with chest pain and nondiagnostic ECGs.     

Selective incorporation of111In-labeled PHOTOFRIN™ by glioma tissuein vivo

The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with¹¹¹In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of¹¹¹In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas.^99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of¹¹¹In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of¹¹¹In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.     

Basal glucose turnover inPsammomys obesus

The aim of this study was to examine wholebody glucose turnover and glucose uptake into individual tissues inPsammomys obesus. The animals were classi-fied according to the level of circulating glucose and insulin in the fed state: group A was normoglycaemic and normoinsulinaemic (glucose <8.0 mmol/l, insulin <150 mU/l), group B was normoglycaemic and hyperinsulinaemic (glucose <8.0 mmol/l, insulin 150 mU/l), and group C was hyperglycaemic and hyperinsulinaemic (glucose 8.0 mmol/l, insulin 150 mU/l). The animals were deprived of food for 6 h, after which they were anaesthetized and cannulated, using the jugular vein for infusions and the carotid artery for blood sampling. Whole-body glucose turnover was measured using a primed-continuous infusion of 6-[³H]-glucose and saline to quantitatively assess hepatic glucose production (HGP), glucose disposal (Rd), and the metabolic clearance rate of glucose (MCR). Following the 2-h infusion period, the glucose metabolic index (Rg) of individual tissues was measured using a fixed-dose bolus of 2-deoxy-[¹⁴C]glucose. Under the steady-state conditions of the experiment, HGP was assumed to be equal to Rd, and both variables were found to be significantly correlated to the fasting glucose concentration (r=0.534,P<0.05,n=19). On the other hand, MCR was found to be inversely correlated to the fasting plasma glucose concentration (r=0.670,P<0.01,n=19). When the animals were divided into three groups as described above, HGP in group C animals was significantly elevated compared with group A (20.8±2.6 vs 12.7±0.6 mg · kg^–1 · min^–1;P<0.05), and MCR showed a tendency to be lower in group C than group A, although the difference was not statistically significant. HGP and MCR were not significantly different between groups A and B. Measurement of the glucose metabolic index in individual tissues showed that group C animals had significantly higher Rg values in muscles and adipse tissues compared with those in group A (P<0.05). In addition, Rg in group B white gastrocnemius and soleus were significantly higher than in group A despite similar rates of HGP and levels of glycaemia. These findings suggest that an early increase in skeletal muscle glucose uptake and hyperinsulinaemia can be demonstrated in group BPsammomysobesus before significant hyperglycaemia.     

Genetic epidemiological study of schizophrenia in Palau, Micronesia: prevalence and familiality

We are studying the genetic etiology of schizophrenia in the Republic of Palau, a remote island nation in Micronesia that has been geographically and ethnically isolated for approximately 2,000 years. The first epidemiological phase sought to estimate the lifetime prevalence of schizophrenia and evaluate the familiality of the illness based on complete ascertainment of cases and families segregating schizophrenia. A total of 160 strictly defined cases of schizophrenia were ascertained in a population of 13,750 adults who were 15 years of age and older. The lifetime prevalence of strictly defined schizophrenia in Palau was 1.99% overall and 2.77% in males vs. 1.24% in females. This greater than 2:1 male-to-female risk ratio for schizophrenia was accompanied by an earlier mean age of onset for males (23.3 years) than for females (27.5 years). These 160 cases of strict schizophrenia represent 59 separate families each identified by a single common founder. Eleven of these families have 5 to 14 cases and represent nearly half of the strict schizophrenia cases in Palau. Although schizophrenia is clearly aggregating in these 11 families, cases are distributed sparsely throughout the large sibships. In the entire sample of 160 cases of strict schizophrenia, there were only 11 sib-pairs and 2 sib-trios. When a family was defined to include third-degree relatives, only 11 cases (6.9%) were nonfamilial. The majority of the ascertained cases can be linked together into extended pedigrees with complex multilineal inheritance patterns. These intricately interconnected families may pose challenges for traditional linkage techniques. However, these Palauan families represent a valuable resource for studying the genetic etiology of schizophrenia because there may be fewer susceptibility genes for schizophrenia in this genetic isolate than in the heterogeneous populations that are common throughout the world today.     

Why obstetric epidurals fail: a study of epidurograms

In a study of the factors involved in the occasional failure of continuous obstetric epidural blockade, contrast injections through epidural catheters and radiographic screening were undertaken in 35 postpartum patients. The two major causes of inadequate block were found to be transforaminal escape of the catheter tip, and persistent unilateral block associated with an obstructive barrier in the epidural space. Recommendations for overcoming these problems are discussed.     

Accumulation and metabolism of carbon-14 labeled benzene,naphthalene, and anthracene by young coho salmon (Oncorhynchus kisutch)

Carbon-14 labeled benzene, naphthalene, and anthracene were administered to young coho salmon (Oncorhynchus kisutch) in the food and by intraperitoneal injection. Regardless of the mode of application the accumulated carbon-14 (% administered dose) in key organs (e.g., liver and brain) increased in the order anthracene > naphthalene > benzene over various time periods. The metabolic fate of the hydrocarbons after intraperitoneal injection was studied. It was shown that the highest percentages of metabolites occurred in the gall bladder; however, significant amounts were also found in the liver, brain, flesh, and carcass. Solvent partition and thin-layer chromatographic techniques were developed to determine the structure of individual metabolites. In brain, liver, and gall bladder, 1-naphthol and 1-naphthyl glucuronic acid were major products of naphthalene metabolism; however, glycoside/sulfate fractions and mercapturic acid were indicated. The heart and flesh were rich in 1-naphthol and the former organ contained significant amounts of 1,2-dihydro-1,2-dihydroxynaphthalene. The findings indicated that the aromatic hydrocarbons in key organs increased in relation to the number of benzenoid rings. Further, it appears that aromatic metabolites are broadly distributed throughout fish exposed to polynuclear aromatic hydrocarbons.