YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an integrated resource for protein information.

The BioKnowledge Library is a relational database and web site (http://www.proteome.com) composed of protein-specific information collected from the scientific literature. Each Protein Report on the web site summarizes and displays published information about a single protein, including its biochemical function, role in the cell and in the whole organism, localization, mutant phenotype and genetic interactions, regulation, domains and motifs, interactions with other proteins and other relevant data. This report describes four species-specific volumes of the BioKnowledge Library, concerned with the model organisms Saccharomyces cerevisiae (YPD), Schizosaccharomyces pombe (PombePD) and Caenorhabditis elegans (WormPD), and with the fungal pathogen Candida albicans (CalPD). Protein Reports of each species are unified in format, easily searchable and extensively cross-referenced between species. The relevance of these comprehensively curated resources to analysis of proteins in other species is discussed, and is illustrated by a survey of model organism proteins that have similarity to human proteins involved in disease.

One-year survival after out-of-hospital cardiac arrest in Copenhagen according to the 'Utstein style'.

OBJECTIVE: To determine survival after out-of-hospital cardiac arrest (CA) in Copenhagen, according to the Utstein recommendations, and compare this with other emergency medical services systems. DESIGN: Register-based cohort study. SETTING: Copenhagen, population 465000, area 90 km(2). PATIENTS: Consecutive group of patients with out-of-hospital CA occurring between January 1 1991 and December 31 1993, followed up via the hospital database systems. MATERIALS: Two specially equipped advanced life support (ALS) units, staffed with an anaesthesiologist and a specially trained fireman, operating to support basic life support units. RESULTS: Of 2225 patients who were unconscious without a pulse or breathing, 1461 were declared dead by the anaesthesiologist. Advanced cardiac life support was initiated in 764, 61 of which were of non-cardiac aetiology. The presumed aetiology was cardiac in 703: in 235 the event was unwitnessed, in 464 witnessed and in four the information was missing. Of 464 witnessed CA the initial rhythm was asystole in 72 cases, in 302 ventricular fibrillation (VF) or ventricular tachycardia (VT), and in 90 were in other rhythms. In these subgroups discharged rates were 5 (7%), 62 (21%) and 1 (1%), and 1-year survival rates were 4 (6%), 49 (16%) and 1 (1%), respectively. The median ALS call-response interval was 6 min. CONCLUSIONS: Survival after CA is more likely if the collapse was witnessed and in patients with VF/VT of cardiac aetiology.

The highly conserved, coregulated SNO and SNZ gene families in Saccharomyces cerevisiae respond to nutrient limitation.

SNZ1, a member of a highly conserved gene family, was first identified through studies of proteins synthesized in stationary-phase yeast cells. There are three SNZ genes in Saccharomyces cerevisiae, each of which has another highly conserved gene, named SNO (SNZ proximal open reading frame), upstream. The DNA sequences and relative positions of SNZ and SNO genes have been phylogenetically conserved. This report details studies of the expression of the SNZ-SNO gene pairs under various conditions and phenotypic analysis of snz-sno mutants. An analysis of total RNA was used to determine that adjacent SNZ-SNO gene pairs are coregulated. SNZ2/3 and SNO2/3 mRNAs are induced prior to the diauxic shift and decrease in abundance during the postdiauxic phase, when SNZ1 and SNO1 are induced. In snz2 snz3 mutants, SNZ1 mRNA is induced prior to the diauxic shift, when SNZ2/3 mRNAs are normally induced. Under nitrogen-limiting conditions, SNZ1 mRNAs accumulate in tryptophan, adenine, and uracil auxotrophs but not in prototrophic strains, indicating that induction occurs in response to the limitation of specific nutrients. Strains carrying deletions in all SNZ-SNO gene pairs are viable, but snz1 and sno1 mutants are sensitive to 6-azauracil (6-AU), an inhibitor of purine and pyrimidine biosynthetic enzymes, and methylene blue, a producer of singlet oxygen. The conservation of sequence and chromosomal position, the coregulation and pattern of expression of SNZ1 and SNO1 genes, and the sensitivity of snz1 and sno1 mutants to 6-AU support the hypothesis that the associated proteins are part of an ancient response to nutrient limitation.

Expressed sequences from conidial, mycelial, and sexual stages of Neurospora crassa.

In the Neurospora Genome Project at the University of New Mexico, expressed sequence tags (ESTs) corresponding to three stages of the life cycle of the filamentous fungus Neurospora crassa are being analyzed. The results of a pilot project to identify expressed genes and determine their patterns of expression are presented. 1,865 partial complementary DNA (cDNA) sequences for 1,409 clones were determined using single-pass sequencing. Contig analysis allowed the identification of 838 unique ESTs and 156 ESTs present in multiple cDNA clones. For about 34% of the sequences, highly or moderately significant matches to sequences (of known and unknown function) in the NCBI database were detected. Approximately 56% of the ESTs showed no similarity to previously identified genes. Among genes with assigned function, about 43.3% were involved in metabolism, 32.9% in protein synthesis and 8.4% in RNA synthesis. Fewer were involved in defense (6%), cell signalling (3.4%), cell structure (3.4%) and cell division (2.6%).

[Malignant bone pain]. / Maligne knoglesmerter.

Bone pain is one of the most frequent causes of pain in patients with cancer, and the levels of metastases and bone pain are not directly correlated. Nociceptors in the periosteum are probably stimulated by halisteresis or by inflammatory oedema leading to an increase in the intraosseous pressure. Some authors believe that the nociceptors in bone are mediated via intraosseous mechanoreceptors in the bone-matrix. At a low pain level the initial treatment is acetylsalicylic acid, paracetamol or other nonsteroidal antiinflammatory drugs. At increasing pain level initial doses of oral opioids are added. In severe bone pain, where conventional therapy seems difficult, opioids are administered by invasive techniques. In localised bone pain palliative radiation is the first treatment of choice. Corticosteroids induce an analgetic effect indirectly by reducing the inflammatory oedema, inhibiting the synthesis of prostaglandins and may inhibit excitatory nerve fibres. Endocrine treatment, calcitonin and biophosphonates have shown a documented pain-relieving effect in patients with disseminated breast and prostate cancer. Chemotherapy has shown a pain-relieving effect in patients with disseminated breast cancer, surgical intervention is used in stabilizing osteolytic bones before or after a fracture ensuring a reasonable relief of pain.

Prehospital care of the burned patient.

For optimal treatment of burns an understanding of the pathophysiological changes occurring locally and systemically after injury is necessary. Accurate estimation of burn size and depth as well as early treatment is essential. Knowledge of the circumstances of the accident and experience in diagnosing physical signs are required in terms of the need for intubation, treatment of poisoning and the occurrence of other trauma.

Orthostatic hypotension during postoperative continuous thoracic epidural bupivacaine-morphine in patients undergoing abdominal surgery.

Fifty patients undergoing colonic surgery received combined thoracic epidural and general anesthesia followed by continuous epidural bupivacaine 0.25% and morphine 0.05 mg/mL, 4 mL/h, for 96 h postoperatively plus oral tenoxicam 20 mg daily. Heart rate (HR) and arterial blood pressure (BP) were measured at supine rest, during orthostatic stress, and after walking prior to and 24, 48, and 72 h and 48 h postoperatively compared to preoperatively (P < or = 0.008); 16 vs 6 patients presented resting systolic BP values < 100 mm Hg (lower range, 70 mm Hg) post- versus preoperatively (P = 0.048). During orthostatic stress the decrease in systolic BP and concomitant increase in HR was similar post- versus preoperatively (BP, P > 0.3; HR, P > 0.34) and 12 vs 8 patient; (P = 0.45) experienced a systolic BP decrease > 20 mm Hg post- versus preoperatively. After walking, systolic BP was significantly lower postoperatively compared with preoperatively (P < or = 0.01). Epidural infusion was discontinued in three patients due to either persisting resting or orthostatic hypotension. There was no correlation between ASA classification, intraoperative bleeding, or postoperative dizziness and incidence of orthostatic hypotension. The results suggest that patients undergoing abdominal surgery and treated with continuous small-dose thoracic epidural bupivacaine-morphine are subjected to a decrease of BP at rest and during mobilization, but not to an extent that seriously impairs ambulation in most patients.

[Perioperative fluid therapy. A quality control study]. / Perioperativ vaeskebehandling. En kvalitetskontrolundersøgelse.

This paper presents a retrospective analysis of the fluid balance during the first 12 hours after laparotomy in 60 consecutive patients. The analysis showed that the majority of patients received greater volumes of crystalloid infusions than recommended, and that the actual number of blood transfusions given did in many circumstances not comply with the available guidelines. Perioperative fluid therapy is an area that needs increased attention since overhydration may contribute to cardiopulmonary morbidity. Perioperative fluid therapy regimens should be evaluated in future prospective, controlled, randomized trials.

Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury.

BACKGROUND: Postoperative pain relief may be improved by reducing sensitization of nociceptive pathways caused by surgical trauma. Such a reduction may depend on the timing and efficacy of analgesia and the duration of the nociceptive block versus the duration of the nociceptive input. We examined whether a prolonged nerve block administered before a superficial burn injury could reduce local inflammation and late hyperalgesia after recovery from the block. METHODS: The effects of a preemptive saphenous nerve block on primary and secondary hyperalgesia, skin erythema, and blister formation, were compared to the opposite unblocked leg for 12 h after bilateral thermal injuries (15 x 25 mm, 49 degrees C for 5 min) in 20 healthy volunteers. Recovery from the block was identified by return of sensation to cold. RESULTS: Six subjects were excluded because of insufficient initial block (2 subjects) or because the block lasted beyond the study period (4 subjects). The remaining 14 subjects experienced significantly reduced primary (P = 0.005) and secondary hyperplasia (P = 0.01) in the blocked leg after return of cold sensation compared to the unblocked leg. Erythema intensity and blister formation were not significantly affected by the blockade (P = 0.94 and P = 0.07, respectively). CONCLUSIONS: These data suggest that a prolonged, preemptive nerve block reduced late hyperalgesia after thermal injury, whereas the erythema and blister formation were not significantly affected.

Stationary phase in Saccharomyces cerevisiae.

Like other microorganisms, the yeast Saccharomyces cerevisiae responds to starvation by arresting growth and entering stationary phase. Because most microorganisms exist under conditions of nutrient limitation, the ability to tolerate starvation is critical for survival. Molecular analyses have identified changes in transcription, translation, and protein modification in stationary-phase cells. At the level of translation, the pattern of newly synthesized proteins in stationary-phase cells is surprisingly similar to the pattern of proteins synthesized during exponential growth. When limited for different nutrients, yeast strains may not enter stationary phase but opt for pathways such as pseudohyphal growth. If nutrient limitation continues, the end-point is likely to be a stationary-phase cell. Based on the results of recent studies, we propose a model for entry into stationary phase in which G(o) arrest is separable from acquisition of the ability to survive long periods of time without added nutrients.

[Treatment of severe hypovolemia with hypertonic saline]. / Behandling af svaer hypovolaemi med hypertont saltvand.

Hypertonic saline (HS) has been used since 1980 in the treatment of traumatised, hypotensive patients. Studies show more pronounced and stable increments in blood pressure and reduced mortality in various subgroups of patients treated with HS compared to isotonic fluids. When infused in the setting of hypovolaemia HS instantaneously expands plasma volume and improves central haemodynamics through increased filling pressures and direct myocardial stimulation. HS, as compared to isotonic fluids, causes precapillary vasodilation, reduction of cell oedema and decreased haematocrit and hence improves regional and capillary perfusion. Furthermore HS-infusion has been shown to attenuate reperfusion injury and restore cell function in cells damaged during hypovolaemic shock. Animal experiments as well as clinical studies on the use of HS are reviewed. A short description of the pathophysiology of acute hypovolaemic shock and exchange of fluids between body compartments is given.

[Hypertonic saline in the treatment of hypovolemia]. / Hypertont saltvand til behandling af hypovolaemi.

Following infusion of hypertonic saline, interstitial and intracellular fluids are within minutes drawn into the vascular compartment as a result of osmotic gradients. Administration of 5 ml/kg body weight hypertonic saline leads to a degree of plasma expansion corresponding to 8-12 ml/kg. Results from major randomized studies on treatment of acute hypotension demonstrate that infusion of hypertonic saline leads to improved survival. Two case reports of patients suffering from severe septicaemia are presented in which infusion of hypertonic saline (7.5%) was performed in order to stabilize haemodynamic parameters. Case report no. I illustrates the rapid plasma expanding properties of hypertonic saline and no. II the effect on central haemodynamics with increased stroke volume and cardiac index. Consequently, hypertonic saline is considered an important supplement in the treatment of severe hypovolaemic or septic shock.

[Continuous subcutaneous infusion of opioids in cancer patients]. / Kontinuerlig subkutan opioidinfusion til cancerpatienter.

This review article describes pharmacokinetics, pharmaco-dynamics, side effects and the practical use of continuous subcutaneous infusion of opioids in cancer patients with pain. Clinical studies have shown that the analgesic effects of continuous subcutaneous infusion of morphine are comparable to continuous intravenous morphine, and that the treatment modality is associated with a low frequency of side-effects and complications. Continuous subcutaneous infusions of morphine are therefore recommended as the treatment of choice for cancer patients with pain, when oral analgesic treatment is no longer possible.

Recovery after laparoscopic colonic surgery with epidural analgesia, and early oral nutrition and mobilisation.

The rate of postoperative recovery is determined by pain, stress-induced organ dysfunction, and limitations in conventional postoperative care. We attempted to provide "stress-free" colonic resection for neoplastic disease in eight elderly high-risk patients by a combination of laparoscopically assisted surgery, epidural analgesia, and early oral nutrition and mobilisation. Effective pain relief allowed early mobilisation, and hospital stay was reduced to 2 days without nausea, vomiting, or ileus. Postoperative fatigue and impairment in functional activity were avoided. Major advances in postoperative recovery can be achieved by early aggressive perioperative care in elderly high-risk patients undergoing colonic surgery.

Use of Z-skin plasty in scar revisions and skin contractures of the lower extremity.

A discussion of the design and use of the Z-skin plasty to revise scars and lengthen skin contractures of the lower extremities is presented. One of the most commonly used rotational flaps to alter scar direction or relieve tension on the existing scar or skin, the Z-plasty can also be the most difficult to perform and carries a high risk of flap loss if inaccurately planned or poorly placed. Several variations of the standard procedure and examples of common usage are presented.

[Acute pain service--another in-hospital specialty?]. / Akut smerteservice--endnu en udspecialisering i hospitalet?

Realizing that achievement in postoperative pain treatment was not satisfactory, central health authorities in USA, United Kingdom and Australia have published guidelines for managing acute pain. Establishing acute pain services is thought to be one of the means of improving pain relief in the individual patient. Development and research are secured and achieved results may be presented currently. At this moment, introduction of acute pain services is at a preliminary stage in Denmark, and consequently an overview of results obtained from abroad is given including pain treatment techniques, management and safety measures, as well as visions concerning the impact of optimal pain relief upon convalescence. We conclude that the introduction of acute pain services is bound to optimize postoperative patient care and might well prove to be a significant factor in reducing postoperative morbidity.

Direct spinal effect of intrathecal and extradural midazolam on visceral noxious stimulation in rabbits.

We measured alterations in a noxious visceromotor reflex in rabbits subjected to intestinal distension, after i.m., extradural or intrathecal injection of midazolam or saline. Spinal catheters were inserted and tunnelled surgically and the animals allowed to recover for 2 weeks. A balloon catheter was placed in the distal part of the descending colon, in the awake rabbit. Intraluminal pressures were increased continuously by water instillation until a sudden withdrawal of the pelvis was observed. Pressure values at withdrawal threshold were recorded immediately before the injection and after 5, 15 and 30 min. Pain thresholds were unaltered after saline. Extradural midazolam 12.5-250 micrograms kg-1 produced a dose-dependent increase in the percent maximum possible effect ranging from 7% after the smallest dose to 80%. Similar dose-dependent effects were observed after intrathecal injection of midazolam 25-62.5 micrograms kg-1. Extradural and intrathecal, but not i.v. injection of flumazenil 25 micrograms kg-1 (a benzodiazepine receptor antagonist) reduced the antinociceptive effect of extradural and intrathecal midazolam to pretreatment levels. A segmental effect of intrathecal midazolam was demonstrated using transcutaneous electrical stimulation in the areas of the neck and the lower back. The effect of intrathecal midazolam 62.5 microrgrams kg-1 was restricted to the lumbar region, demonstrating a selective action on the spinal cord. Thus extradural and intrathecal midazolam produced a dose-dependent effect on the reflex response to visceral distension in rabbits. This effect is caused by a direct spinal action on benzodiazepine receptors in the spinal cord.

Body mass and weight as indicators for cholesterol screening.

BACKGROUND: Universal screening of serum cholesterol levels in adults has been recommended but not achieved. We were interested in factors that affected screening rates, and whether obese patients were more likely to have elevated cholesterol levels than other patients in our practice. METHODS: A sequential sample of charts was reviewed for height, weight, race, sex, diagnosis of hypertension or diabetes, and evidence of cholesterol screening. RESULTS: Of 604 adult patients, 32% had serum cholesterol measurements. No correlation was found between weight or body mass index and cholesterol levels. Patients with hypertension or diabetes were more frequently screened. Sex and race did not influence screening rates. CONCLUSIONS: In this population neither weight nor body mass index was associated with elevated serum cholesterol levels, suggesting that screening must be offered without regard to level of obesity in order to find those patients who will benefit from intervention.

Recovery after total intravenous anaesthesia using combined midazolam/alfentanil infusion and reversal with flumazenil.

One of the major problems with total intravenous anaesthesia (TIVA) is postoperative sedation, possibly with respiratory depression. The aim of the present study was to evaluate the recovery characteristics after TIVA using a continuous infusion of a mixture of midazolam and alfentanil with flumazenil reversal before extubation. This method was compared to balanced anaesthesia using midazolam, alfentanil and nitrous oxide without flumazenil reversal. The degree of sedation was measured by reaction time test, Glasgow Coma Scale, cipher copying test and subtraction test. We found significantly faster reaction times postoperatively in the TIVA group (n = 15) compared to the balanced group (n = 13), despite larger doses of both midazolam (median 21 mg versus 9 mg) and alfentanil (median 5.9 mg versus 4.5 mg). The other tests revealed no difference between the groups. One patient became resedated after flumazenil. We conclude that the TIVA technique described here resulted in slightly better recovery characteristics, offering a usable alternative to balanced anaesthesia.