One scan for all: extended role of cardiac CT angiography in acute myocardial infarction.

BACKGROUND: Cardiac computed-tomographic angiography (CTA) has gained widespread acceptance as a useful non-invasive technique in the assessment of coronary artery disease. Although most interest has focused on coronary vessels, analysis of myocardial perfusion, left ventricular wall motion, ejection fraction and left ventricular structure can easily be performed at the same time allowing comprehensive assessment of anatomy and function in a single examination. We present a case of acute ST elevation myocardial infarction where cardiac catheterization was deferred, but assessment by CTA permitted a management plan to be constructed using rest perfusion and blood pool inversion analyses of the dataset obtained during the coronary artery study. CONCLUSION: Coronary CT angiography can provide a comprehensive assessment of coronary arteries, myocardial perfusion and structural features in those not suitable for coronary angiography after myocardial infarction.

Quality of life in patients with advanced renal cell carcinoma treated with temsirolimus or interferon-alpha.

BACKGROUND: Temsirolimus was approved in Europe as first-line treatment of poor-prognosis advanced renal cell carcinoma (advRCC) based on significant clinical benefits. METHODS: Patients with advRCC and multiple poor-prognostic factors were randomly assigned to receive 25 mg intravenous temsirolimus weekly, interferon-alpha (titrated to 18 mU) three times weekly, or 15 mg intravenous temsirolimus weekly plus 6 mU of interferon-alpha three times weekly. EuroQol-5D utility score (EQ-5D index) and the EQ-5D visual analogue scale (EQ-VAS) responses were recorded. For analysis, patients were required to have their EQ-5D data recorded at baseline, week 12, and last visit after week 12. The analysis was conducted using last-visit data and a repeated-measures mixed-effect (RMME) model to evaluate quality-of-life differences between temsirolimus and interferon-alpha, controlling for baseline covariates. RESULTS: Average EQ-5D score at the last measure was significantly higher in patients receiving temsirolimus compared with interferon-alpha: by 0.10 on EQ-5D index (P=0.0279) and by 6.61 on EQ-VAS (P=0.0095). In the RMME model, the least-square mean for on-treatment EQ-5D index score was 0.590 with temsirolimus and 0.492 with interferon-alpha (P=0.0022). CONCLUSION: Temsirolimus is associated with significantly higher EQ-5D scores compared with interferon-alpha in patients with previously untreated poor-prognosis advRCC.

Constriction infection.

Chronic constrictive pericarditis (CCP) is a clinical syndrome caused by compression of the heart due to a thickened or rigid pericardium. In the affluent West, the majority of cases of CCP are neither tuberculous nor calcific. In an American cohort undergoing pericardectomy for the condition, only 27% had calcification and under 10% had TB [1]. As a result, pericardial calcification (PC) as a marker of CCP has become neglected. We present a 48-year-old male admitted with atrial flutter, acute chest infection and signs of right heart congestion. PC was documented one year previously on a non-contrast CT chest. On this occasion, cardiac catheterisation confirmed hemodynamically significant CCP and cardiac magnetic resonance (cMR) study showed contiguous mass lesions in the pericardium, compression of the right ventricle, enlargement of the right atrium, hepatic enlargement and a pneumonic process in the left lung. He was commenced on antibiotics and anti-tuberculous therapy with a diagnosis of bacterial super-infection of tuberculous CCP. This was confirmed at pericardectomy along with an infected fistula into the left lung. Any finding of PC should be followed up with a thorough haemodynamic and anatomical assessment using any of a wide range of non-invasive imaging modalities.

Enhanced trehalose production improves growth of Escherichia coli under osmotic stress.

The biosynthesis of trehalose has been previously shown to serve as an important osmoprotectant and stress protectant in Escherichia coli. Our results indicate that overproduction of trehalose (integrated lacI-Ptac-otsBA) above the level produced by the native regulatory system can be used to increase the growth of E. coli in M9-2% glucose medium at 37 degrees C to 41 degrees C and to increase growth at 37 degrees C in the presence of a variety of osmotic-stress agents (hexose sugars, inorganic salts, and pyruvate). Smaller improvements were noted with xylose and some fermentation products (ethanol and pyruvate). Based on these results, overproduction of trehalose may be a useful trait to include in biocatalysts engineered for commodity chemicals.

Gene array-based identification of changes that contribute to ethanol tolerance in ethanologenic Escherichia coli: comparison of KO11 (parent) to LY01 (resistant mutant).

Escherichia coli KO11 (parent) and LY01 (mutant) have been engineered for the production of ethanol. Gene arrays were used to identify expression changes that occurred in the mutant, LY01, during directed evolution to improve ethanol tolerance (defined as extent of growth in the presence of added ethanol). Expression levels for 205 (5%) of the ORFs were found to differ significantly (p < 0.10) between KO11 and LY01 under each of six different growth conditions (p < 0.000001). Statistical evaluation of differentially expressed genes according to various classification schemes identified physiological areas of importance. A large fraction of differentially expressed ORFs were globally regulated, leading to the discovery of a nonfunctional fnr gene in strain LY01. In agreement with a putative role for FNR in alcohol tolerance, increasing the copy number of fnr(+) in KO11(pGS196) decreased ethanol tolerance but had no effect on growth in the absence of ethanol. Other differences in gene expression provided additional clues that permitted experimentation. Tolerance appears to involve increased metabolism of glycine (higher expression of gcv genes) and increased production of betaine (higher expression of betIBA and betT encoding betaine synthesis from choline and choline uptake, respectively). Addition of glycine (10 mM) increased ethanol tolerance in KO11 but had no effect in the absence of ethanol. Addition of betaine (10 mM) increased ethanol tolerance by over 2-fold in both LY01 and KO11 but had no effect on growth in the absence of ethanol. Both glycine and betaine can serve as protective osmolytes, and this may be the basis of their beneficial action. In addition, the marAB genes encoding multiple antibiotic resistance proteins were expressed at higher levels in LY01 as compared to KO11. Interestingly, overexpression of marAB in KO11 made this strain more ethanol-sensitive. Overexpression of marAB in LY01 had no effect on ethanol tolerance. Increased expression of genes encoding serine uptake (sdaC) and serine deamination (sdaB) also appear beneficial for LY01. Addition of serine increased the growth of LY01 in the presence and absence of ethanol but had no effect on KO11. Changes in the expression of several genes concerned with the synthesis of the cell envelope components were also noted, which may contribute to increased ethanol tolerance.

Recreational injuries in children: incidence and prevention.

Participation in eight common types of recreational activities leads annually to more than 2 million medically treated musculoskeletal injuries in children aged 5 to 14 years. Many of these injuries could have been prevented if current safety guidelines and protective equipment had been used. Studies have demonstrated the value of safety education programs in preventing injuries. Parents consider their child's physician an important source of safety education, and orthopaedic surgeons have a unique opportunity to provide injury prevention counseling. The American Academy of Orthopaedic Surgeons recognizes the importance of injury prevention and has developed advocacy programs that are readily available to physicians and the public. Individual orthopaedists should be involved in injury prevention through patient education, research, community programs, and regulatory efforts that promote safe play for children.

Doxycycline use for rickettsial disease in pediatric patients.

BACKGROUND: Recent evidence suggests that despite potential side effects, doxycycline should be considered the drug of choice for children of all ages in whom a rickettsial disease is considered in the differential diagnosis of the illness. We hypothesized that doxycycline would be used infrequently for the treatment of suspected rickettsial disease. The objective of the investigation was to determine the initial antibiotic administered to children for whom rickettsial infection was considered likely. METHODS: The study population consisted of 35 children evaluated at Texas Children's Hospital between 1987 and 1999 in whom rickettsial disease was a diagnostic consideration. Demographic information and clinical manifestations were assessed through a retrospective chart review. RESULTS: Thirty children (86%) presented with fever, 21 (60%) with rash and 14 (40%) with headache, which are typical presenting symptoms for rickettsial diseases. Only 1 of 35 children (3%) was prescribed a tetracycline class antibiotic as initial empiric therapy. Eleven (31%) children received doxycycline during the hospital course. A total of 19 patients, or 54%, received an antimicrobial known to have efficacy in the treatment of rickettsial infection, usually at the suggestion of an infectious diseases consultant. CONCLUSIONS: Even among children for whom rickettsial infection is a diagnostic consideration, doxycycline is not prescribed with the frequency that is indicated. Pediatric caregivers should have heightened awareness regarding the appropriate indications for doxycycline use in childhood.

Phase I pharmacokinetic study of the novel antitumor agent SR233377.

SR233377 is a novel thioxanthenone analogue that demonstrated solid tumor selectivity in vitro with activity confirmed in vivo against several murine tumors including those of colon, pancreas, and mammary origin. Its primary preclinical dose-limiting toxicities included myelosuppression and neurological toxicity. The neurological toxicity was acute and could be ameliorated in mice when the drug was administered as a 1-h infusion instead of rapid i.v. injection. As a result of its preclinical efficacy profile, SR233377 entered Phase I clinical investigation. The compound was administered i.v. over 2 h on day 1 repeated every 28 days. The starting dose was 33 mg/m2 (one-tenth the mouse LD10). Escalations continued to 445 mg/m2 (six escalations), where dose-limiting toxicity was observed. At this dose, acute ventricular arrhythmias, including one patient with torsades de pointes and transient cardiac arrest, occurred. Because this toxicity might have been related to the plasma peak, the protocol was amended to a 24-h infusion beginning at 225 mg/m2. With this dose, prolongation of the corrected QT interval (QTc) over the pretreatment levels resulted. Because prolonged QTc is a known forerunner to acute ventricular arrhythmias, clinical development of SR233377 was stopped. However, preclinical antitumor and toxicity studies with analogues are underway with hopes of identifying a new clinical candidate with similar antitumor effects that is devoid of cardiac toxic effects.

Effects of a medicine review and education programme for older people in general practice.

AIMS: To determine whether a medicine review and education programme influences the compliance and knowledge of older people in general practice. METHODS: Older people taking at least three medicines were randomly allocated to a control or intervention group. Both groups received three visits from a clinical pharmacist: Visit 1: Assessment and patients' medicines rationalized in intervention group. Visit 2: Intervention group given medicines education. Visit 3: Knowledge and compliance in both groups assessed by structured questionnaire RESULTS: Compliance in the intervention group was 91.3%, compared with 79.5% in the control group (P < 0.0001). The number of intervention group patients correctly understanding the purpose of their medicines increased from 58% to 88% on the second visit, compared with 67% to 70% in the control group (P < 0.0005). CONCLUSIONS: A general practice based medication review and education programme improved medicine compliance and knowledge of older people in the short term.

Phase I/pharmacokinetic trial of the novel thioxanthone SR233377 (WIN33377) on a 5-day schedule.

PURPOSE: SR233377 (WIN33377) is a novel 4-aminomethyl thioxanthone derivative with promising preclinical activity against solid tumors at doses substantially below the MTD. We performed a phase I trial to determine a suitable phase II dose of SR233377 when administered as a 2-h intravenous infusion for five consecutive days. METHODS: A group of 25 patients with a range of solid tumor diagnoses and good performance status received SR233377 at eight dose levels ranging from 4.8 mg/m2 per day to 74.7 mg/m2 per day. Cycles were repeated every 35 days and patients were evaluated for response following two cycles of treatment. Doses were escalated in cohorts of three using a modified Fibonacci scheme. Pharmacokinetic sampling was performed during the first cycle in all patients. RESULTS: Toxicities of SR233377 on this schedule included neutropenia, fever, nausea, and dyspnea but all were mild and not dose-limiting. Asymptomatic prolongation of the corrected QT (QTc) interval during infusion in all patients monitored at the 74.7 mg/m2 dose level prompted closure of the study. QT lengthening correlated with increasing plasma concentrations of SR233377. SR233377 Cmax values increased linearly with dose, but substantial interpatient variability in SR233377 AUC, clearance, and half-life was noted. There was no evidence of drug accumulation when day 1 and day 5 AUC and Cmax values were compared. Seven patients displayed tumor growth inhibition lasting for 4 months or more. CONCLUSIONS: We conclude that SR233377 administered on a 5-day schedule is associated with tolerable clinical symptoms and some activity against a range of solid tumors but dosing is limited by QTc prolongation, a condition that predisposes to ventricular arrhythmias. Phase II development on this schedule is not recommended based on the occurrence of this concentration-dependent effect. Further investigation of alternative schedules of administration and of SR233377 analogues is warranted.

Transposed basilic vein versus polytetrafluorethylene for brachial-axillary arteriovenous fistulas.

BACKGROUND: Both transposed basilic vein (BV) and polytetrafluorethylene (PTFE) upper arm arteriovenous fistulas (AVF) are common angioaccess operations. To evaluate the patency and complication rates after AVF, a concurrent series of patients was reviewed. METHODS: Ninety-eight patients underwent brachial artery to axillary vein AVF: 30 BV and 68 PTFE. The PTFE grafts were performed in the standard fashion, whereas the basilic veins were translocated subcutaneously to the brachial artery. RESULTS: Risk factors were similar between the two groups. Basilic vein AVF had better patency at 24 months (70% BV versus 46% PTFE, P = 0.023). The dialysis access complications were higher in the BV group (20%) versus PTFE (5%), but the PTFE group had a higher infection rate (10%) than BV (0%). CONCLUSIONS: The primary and secondary patency rates were superior in the BV AVFs. The BV AVF preserves the venous outflow tract after AVF thrombosis for a future PTFE AVF operation.

Northern bobwhites as disease indicators for the endangered Attwater's prairie chicken.

Because of limited access to the endangered Attwater's prairie chicken (Tympanuchus cupido attwateri), we used a related species, the northern bobwhite (Colinus virginianus), as a surrogate for disease evaluation. Free-living northern bobwhites (n = 62) on the Attwater Prairie Chicken National Wildlife Refuge (near Eagle Lake, Texas, USA) were examined during spring and fall 1993 for helminthic endoparasites and specific antibodies against the infectious agents responsible for nine infectious diseases. Trichostrongylus cramae, Raillietina sp., and Strongyloides avium were collected from 97, 44, and 32% of northern bobwhites examined, respectively. Dispharynx nasuta and Syngamus trachea also were found. No gross lesions due to parasites were observed. Specific antibody to Pasteurella multocida was found in 3 of 53 plasma samples. It is possible that potentially pathogenic species such as P. multocida, T. cramae, and D. nasuta could threaten sympatric Attwater's prairie chickens.

Influence of insulin on follicular development and the intrafollicular insulin-like growth factor I (IGF-I) system in sows after weaning.

Twenty-four crossbred primiparous sows were used to investigate the influence of insulin administration after weaning on the intrafollicular insulin-like growth factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1 (n = 4). The number and diameters of ovarian follicles were recorded, and fluid was aspirated from the 20 largest follicles for determination of oestradiol and IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins (IGFBPs) by western ligand blotting. The walls of the follicles were collected for mRNA analysis by RNase protection assay or granulosa cells were collected for estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the number of follicles available on day 5 compared with saline-treated animals (19.8 versus 17.8). The concentration of oestradiol in follicular fluid from large (7-10 mm) follicles on days 3 and 5 was reduced (treatment by size class interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular concentrations of IGF-I at days 3 and 5 after weaning (treatment by day interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass 30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in saline-treated animals but decreased fourfold in insulin-treated sows from day 3 to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a manner consistent with slowing follicular growth and possibly allowed more follicles to become available for ovulation.

Serologic and parasitologic survey of the endangered Attwater's prairie chicken.

Because conservation biologists have postulated that infectious diseases may have potentiated the endangerment of the Attwater's prairie chicken (Tympanuchus cupido attwateri), free-living prairie chickens were surveyed from all remaining populations for helminthic endoparasites and antibody against the etiological agents of nine infectious diseases. Samples from 4 of 27 adult males were positive for anti-Pasteurella multocida antibody. All other serologic tests were negative (n = 19). We identified Dispharynx nasuta, a parasite previously associated with disease in other grouse from North America, in one of three adult Attwater's prairie chickens examined. Evidence of Trichostrongylus cramae was found for eight of nine suitable samples, which represents the first report of this parasite in prairie grouse. The mean intensity of T. cramae in Attwater's prairie chicken was 1,019.3 (Range = 3-1,906; n = 3). Further work is needed to determine whether P. multocida, T. cramae, or D. nasuta are detrimental to Attwater's prairie chicken populations. If so, conservation biologists could reduce the prevalence and incidence of these parasites and potentially gain more time to address the habitat conditions thought to be the ultimate cause of population declines.

Helminths of wintering geese in Texas.

Ten Canada geese (Branta canadensis), 24 snow geese (Chen caerulescens) and 22 white-fronted geese (Anser albifrons) from coastal Texas (USA) were examined for helminths. Three cestode, seven nematode, and three trematode species were collected. Gizzard nematodes (Amidostomum anseris, A. spatulatum and Epomidiostomum crami) infected 53 of 54 birds. Gross lesions were not attributed to helminth infections and the host population does not appear to be impaired by them.