Long-term outcomes of children with symptomatic congenital cytomegalovirus disease.

OBJECTIVE: To assess long-term outcomes of children with symptomatic congenital cytomegalovirus (CMV) disease detected at birth. STUDY DESIGN: We used Cox regression to assess risk factors for intellectual disability (intelligence quotient <70), sensorineural hearing loss (SNHL; hearing level ⩾25 dB in any audiometric frequency) and vision impairment (best corrected visual acuity >20 or based on ophthalmologist report). RESULTS: Among 76 case-patients followed through median age of 13 (range: 0-27) years, 56 (74%) had SNHL, 31 (43%, n=72) had intellectual disability and 18 (27%, n=66) had vision impairment; 28 (43%, n=65) had intellectual disability and SNHL with/without vision impairment. Microcephaly was significantly associated with each of the three outcomes. Tissue destruction and dysplastic growth on head computed tomography scan at birth was significantly associated with intellectual disability and SNHL. CONCLUSION: Infants with symptomatic congenital CMV disease may develop moderate to severe impairments that were associated with presence of microcephaly and brain abnormalities.

Extremophile-inspired strategies for enzymatic biomass saccharification.

Domestic ethanol production in the USA relies on starch feedstocks using a first generation bioprocess. Enzymes that contribute to this industry remain of critical value in new and established markets as commodity additives and for in planta production. A transition to non-food feedstocks is both desirable and essential to enable larger scale production. This objective would relieve dependence on foreign oil and strengthen the national economy. Feedstocks derived from corn stover, wheat straw, perennial grasses and timber require pretreatment to increase the accessibility of the cellulosic and hemicellulosic substrates to commodity enzymes for saccharification, which is followed by fermentation-based conversion of monosaccharides to ethanol. Hot acid pretreatment is the industrial standard method used to achieve deconstruction of lignocellulosic biomass. Therefore, enzymes that tolerate both acid and heat may contribute toward the improvement of lignocellulosic biomass processing. These enzymes are produced naturally by extremely thermophilic microbes, sometimes called extremophiles. This review summarizes information on enzymes from selected (acido)thermophiles that mediate saccharification of alpha- and beta-linked carbohydrates of relevance to biomass processing.

A silica long base tiltmeter with high stability and resolution.

In order to be able to provide valuable data in multiparameter measurement field operations, tiltmeters need to have a noise level better or equal than 10(-9) rad for a period range from a few minutes to a few years and a long term stability ranging from 10(-7) to 10(-8) rad/yr. Tiltmeter measurements should also be as much as possible insensitive to thermal disturbances, by taking great care of the horizontality of the base line tube first. Secondly, thermal responses have been assessed. We also took great care of the coupling of our tiltmeters with the bedrock. We've designed a long base tiltmeter with sensors in silica which has a low dilatation coefficient. The linear variable displacement transducer is based on coil coupling (powered by an alternative voltage). Finally we show the results of two 100 m silica water tube tiltmeters which were installed in a mine in the French Vosges massif in the framework of a hydrology research project. These instruments show a remarkably good stability (6.5x10(-9) rad/month) and a low noise level (of the order of 10(-11) rad). Toroidal and spheroidal free modes of the Earth were observed after the two last major earthquakes on Sumatra.

Peripheral nerve stimulation for the treatment of chronic pain.

The aim of this retrospective study is to evaluate the role of the implanted peripheral nerve stimulator in patients with pain in a peripheral nerve distribution. The current study is the largest in the literature that examines the role of the implantable peripheral nerve stimulator in the chronic pain patient. Our patient sample included 38 patients (with 41 nerve stimulators), consisting of 19 males and 19 females with a mean age of 44 years (SD=11 years). Four groups of etiologic factors were identified; blunt or sharp nerve trauma (14/38), iatrogenic injuries from surgery (9/38), inadvertent injection of a nerve (9/38) and post surgery for entrapment or tumour (8/38). Stimulation was attempted in 45 patients, but an initial trial failed in 4. Mean follow-up time from implantation of the stimulator was 31 months (SD=19 months). Compensation benefit was an issue in 29 cases (76%). Outcome following implantation was assessed based on pain criteria, narcotic usage and return to normal function/ work. Relief from preoperative pain was judged as good (>50% relief) by 23/38 patients (61%). A total of 15 patients reported fair or poor results (39%). Six patients required removal of their stimulators (15%) due to infection or reduction of pain control after an initial good result. A statistically significant decrease in reported pain level was found postoperatively (p<0.05). Workers' compensation patients have equivalent outcomes to non-compensable patients (p>0.05). Eighteen of 38 (47%) patients reported a significant improvement in their activity levels following stimulator implant. In conclusion, over 60% of patients had a significant improvement in their pain and lifestyle following implantation of peripheral nerve stimulators. We therefore conclude that peripheral nerve stimulation can be useful in decreasing pain in well selected patients with severe pain in the distribution of a peripheral nerve.

[Translational research in renal cell cancer. Illustrated by the example of the vascular endothelial growth factor pathway]. / Translation molekularer Zusammenhänge in die klinische Anwendung. Dargestellt am Beispiel des Vascular-Endothelial-Growth-Factor- (VEGF-)Pathway.

For patients with metastatic renal cell cancer (RCC), therapeutic options after cytokine failure are rather limited. There is a considerable need to identify new substances for systemic therapy. Due to upregulation after the loss of a functional von Hippel Lindau gene product, the vascular endothelial growth factor (VEGF) pathway is a promising target for a molecular based therapy. Over the last few years, therapeutic agents have been developed which inhibit this pathway at various levels. Here, we provide an overview of the molecular background and currently used drugs which have entered clinical trials in the setting of metastatic RCC disease. Until now, the results from early clinical trials are very promising, however, the best schedule, dosage, potential combination regimens, as well as long time efficacy, are still to be determined.

Post anaesthesia care unit discharge: a clinical scoring system versus traditional time-based criteria.

This prospective cohort analysis compared the efficiency of time-based discharge criteria (Group 1) to a modified clinical scoring system (Group 2), incorporating the assessment of pain and temperature, in the post anaesthesia care unit (PACU). Two consecutive series of patients (n = 292) were assessed following general anaesthesia for various surgical procedures. The time taken for patients to satisfy their respective discharge criteria was recorded as PACU length of stay (LOS). Patient group and other factors that may have influenced PACU-LOS were examined using time-to-event analysis. The raw PACU-LOS was not shown to be different between the two groups (log rank test, P = 0.12). Covariate adjusted estimates were used to compare the two discharge criteria and also to identify other factors influencing PACU-LOS. The Cox regression model was poorly specified and a log-logistic accelerated failure time model was found to be the most parsimonious predictive model. Predictors of decreased PACU-LOS were the treatment group (Group 2 versus Group 1) and the covariate recording anaesthetic airway choice (no endotracheal tube (ETT) versus ETT). Surgical time, as a linear function, intra- and postoperative opioid administration, as well as postoperative antiemetic use were predictors of increased PACU-LOS. Patient age, gender, urgency of surgery, and ASA classification were not predictive of PACU-LOS. Using covariate adjusted estimates, the new PACU discharge criteria, based on the Aldrete's scoring system, was associated with a significantly reduced PACU-LOS in comparison with time-based criteria.

Barriers to effective perioperative communication in indigenous Australians: an audit of progress since 1996.

This prospective study was designed to elucidate barriers limiting effective perioperative communication between indigenous Australians and anaesthetists, and to identify strategies for improving communication. A questionnaire was used to collect data on 1040 consecutive patients undergoing anaesthesia at Royal Darwin Hospital between February and March 2003. 27.1% of these patients described themselves as Aboriginal. Aboriginal patients were more likely to undergo emergency surgery and were more likely to be classified as ASA 3, 4 or 5 than non-indigenous patients. Communication difficulties were identified in 28.7% of all Aboriginal patients, which was 31 times higher than those in non-Aboriginal patients. The most common reason identified for this was difficulty in speaking English. Only 17.7% of Aboriginal patients presenting to the operating theatre spoke English as their first language. Unfortunately, the anaesthetic team utilized the Aboriginal interpreter service in only a minority of cases. Communication difficulty in indigenous Australians is pervasive and often goes unrecognized. The results suggest that heath care providers may need staff training in cross-cultural communication and that protocols need to be developed within the health care system so that interpreters are called upon automatically early in the admission process.

The role of anaesthetists in the Darwin response to the Bali bombing.

The bombing of nightclubs in Bali on the night of October 12, 2002 was one of the worst peacetime disasters affecting Australians. This paper examines the unique role of anaesthetists in helping manage the victims, with the main emphasis on events in Darwin. Anaesthetists were involved in the multiple stages of patient care; from the hospital in Bali, evacuation to Darwin, resuscitation and onward evacuation to burns units around Australia as well as definitive surgical management. We discuss the role of anaesthetists in disaster management.

Treatment of painful peripheral neuroma by vein implantation.

Painful neuromas form on cutaneous nerves as a result of trauma, pressure, stretch or entrapment. Since the earliest descriptions of neuromas, proposed treatments have been met with poor results and controversy. The myriad of treatments described include: simple division of an affected nerve, implantation into muscle or bone, silicon sleeves and caps, repeated injection of steroids, end-to-side neurorrhaphy, medication and vein caps to name a few. Due to encouraging recent reports of treatment of painful neuromas by vein implantation, the authors describe a simple technique to achieve this surgical goal. As veins are readily accessible due to their proximity in the neurovascular bundle, they serve as a ready source for grafting. The advantages include minimisation of trauma to bone and muscle as compared with previous treatment techniques and the relative ease of the method.

Posterior femoral cutaneous nerve entrapment neuropathy: operative exposure and technique.

An isolated posterior femoral cutaneous nerve lesion is rare. There have been seven reported cases to date. We report a 51-year-old male with pain in the posterolateral thigh, atypical from the classic anatomical description. Somatosensory evoked potentials were suggestive of a posterior femoral cutaneous nerve lesion. We describe our operative exposure and technique for decompression of the posterior femoral cutaneous nerve and include a comparative anatomical explanation for the unusual area of our patient's pain.

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Severe falciparum malaria in five soldiers from East Timor: a case series and literature review.

Despite chemoprophylaxis, malaria remains a serious threat for large numbers of non-immune soldiers deployed in endemic areas. Five adult cases of severe falciparum malaria are reported. Three cases were complicated by multiorgan failure and one of these patients died from cerebral malaria. These cases serve to highlight issues, in an Australian intensive care unit, associated with the management of severe malaria, an uncommon disease in our country. The need for rapid diagnosis and commencement of appropriate treatment is paramount in preventing further morbidity and mortality. Understanding and management of malaria continues to evolve rapidly. The pathophysiology of acute lung injury, shock and brain injury associated with malaria are examined in light of recent research. This article discusses the current controversies of exchange blood transfusion and the use of the new artemisinin derivatives.

Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells.

Wilson's disease, a genetic copper-overload condition, is currently treated with zinc because of the ability of zinc to induce metallothionein. We are interested in nonmetal chemicals that may alter intestinal copper metabolism and thus help to alleviate copper toxicity. Previously, we have shown that quercetin, a dietary flavonoid, can chelate copper. This study further examined the interaction of quercetin and copper in intestinal epithelial cells. We found that quercetin enhanced metallothoinein induction by copper and the effect was dose dependent. Quercetin also exerted a cumulative effect after repeated exposure. Repeated low-dose treatment (3-10 microM) of cells with quercetin can lead to the same effect on metallothoinein as one higher concentration treatment (100 microM). This property of quercetin is distinct from its chemical interaction with copper, but both can contribute to a reduction of copper toxicity. Among other flavonoids tested, two other copper chelators, catechin and rutin, did not increase copper induction of metallothionein, whereas genistein, an isoflavone that does not interact with copper chemically, increased copper induction of metallothionein. The effect of quercetin on copper metabolism is unique. Quercetin decreased zinc-stimulated metallothionein expression and had no effect on the cadmium induction of metallothionein. The clinical application of our observation needs to be explored.

Secreted euryarchaeal microhalocins kill hyperthermophilic crenarchaea.

Few antibiotics targeting members of the archaeal domain are currently available for genetic studies. Since bacterial antibiotics are frequently directed against competing and related organisms, archaea by analogy might produce effective antiarchaeal antibiotics. Peptide antibiotic (halocin) preparations from euryarchaeal halophilic strains S8a, GN101, and TuA4 were found to be toxic for members of the hyperthermophilic crenarchaeal genus Sulfolobus. No toxicity was evident against representative bacteria or eukarya. Halocin S8 (strain S8a) and halocin R1 (strain GN101) preparations were cytostatic, while halocin A4 (strain TuA4) preparations were cytocidal. Subsequent studies focused on the use of halocin A4 preparations and Sulfolobus solfataricus. Strain TuA4 cell lysates were not toxic for S. solfataricus, and protease (but not nuclease) treatment of the halocin A4 preparation inactivated toxicity, indicating that the A4 toxic factor must be a secreted protein. Potassium chloride supplementation of the Sulfolobus assay medium potentiated toxicity, implicating use of a salt-dependent mechanism. The utility of halocin A4 preparations for genetic manipulation of S. solfataricus was assessed through the isolation of UV-induced resistant mutants. The mutants exhibited stable phenotypes and were placed into distinct classes based on their levels of resistance.

Autohydrolysis of plant polysaccharides using transgenic hyperthermophilic enzymes.

Commercial bioprocessing of plant carbohydrates, such as starch or cellulose, necessitates the use of commodity enzyme additives to accelerate polysaccharide hydrolysis. To simplify this procedure, transgenic plant tissues constitutively producing commodity enzymes were examined as a strategy for accelerating carbohydrate bioprocessing. Hyperthermophilic glycosyl hydrolases were selected to circumvent enzyme toxicity, because such enzymes are inactive at plant growth temperatures and are therefore physiologically benign. Transgenic tobacco lines were established that produced either a hyperthermophilic alpha-glucosidase or a beta-glycosidase using genes derived from the archaeon Sulfolobus solfataricus. Western blot and immunoprecipitation analyses were used to demonstrate the presence of recombinant enzymes in plant tissues. Transgenic enzyme levels exhibited an unusual delayed pattern of accumulation while their activities survived plant tissue preservation. Transgenic plant protein extracts released glucose from purified polysaccharide substrates at appreciable rates during incubation in high-temperature reactions. Glucose was also produced following enzymatic treatment of plant extracts enriched for endogenous polysaccharides. Direct conversion of plant tissue into free sugar was evident using whole plant extracts of either transgenic line, and could be significantly accelerated in a synergistic manner by combining transgenic line extracts.

Bacterial growth state distinguished by single-cell protein profiling: does chlorination kill coliforms in municipal effluent?

Municipal effluent is the largest reservoir of human enteric bacteria. Its public health significance, however, depends upon the physiological status of the wastewater bacterial community. A novel immunofluorescence assay was developed and used to examine the bacterial growth state during wastewater disinfection. Quantitative levels of three highly conserved cytosolic proteins (DnaK, Dps, and Fis) were determined by using enterobacterium-specific antibody fluorochrome-coupled probes. Enterobacterial Fis homologs were abundant in growing cells and nearly undetectable in stationary-phase cells. In contrast, enterobacterial Dps homologs were abundant in stationary-phase cells but virtually undetectable in growing cells. The range of variation in the abundance of both proteins was at least 100-fold as determined by Western blotting and immunofluorescence analysis. Enterobacterial DnaK homologs were nearly invariant with growth state, enabling their use as permeabilization controls. The cellular growth states of individual enterobacteria in wastewater samples were determined by measurement of Fis, Dps, and DnaK abundance (protein profiling). Intermediate levels of Fis and Dps were evident and occurred in response to physiological transitions. The results indicate that chlorination failed to kill coliforms but rather elicited nutrient starvation and a reversible nonculturable state. These studies suggest that the current standard procedures for wastewater analysis which rely on detection of culturable cells likely underestimate fecal coliform content.